The objective of the proposed research is to study the interactions or symbiotic relationships involving members of the normal, indigenous microflora and the human body. Spirpchetes, which inhabit several regions of the healthy human body, will be used as a tool or model to gain information on the physiological, ecological, and ultrastructural factors involved in associations or symbioses between humans and indigenous microorganisms. We intend to study the physiological interactions between the human body and spirochetes which are normal inhabitants of the gingival crevice and interproximal areas of teeth, of the intestinal mucosa, and of the external genitalia. The interrelationships between these spirochetes and the indigenous microflora sharing the same habitats will be investigated. These studies are expected to contribute to the understanding of infectious processes in which the indigenous microflora participates. A major goal of the proposed research is to elucidate the biochemical factors responsible for the dependency of indigenous spirochetes on their human host. Spirochetes and indigenous bacteria with which they are associated will be isolated from diverse habitats within the human body, their physiology will be studied, and experiments will be conducted to clarify the contributions made by the human body to the survival or growth of these microorganisms. Investigation of the dependency of indigenous spirochetes on their human host should serve to clarify aspects of the close association between the human body and pathogenic spirochetes (e.g., Treponema pallidum) or opportunistic spirochetes which participate in mixed infections.